Wide phenotypic variations in Charcot-Marie-Tooth 1A neuropathy with rare copy number variations on 17p12

Sumaira Kanwal,최병옥,김상범,구해수,김지영,현영세,이혜진,정기화 한국통합생물학회 2011 Animal cells and systems Vol.15 No.4

Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A)neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n=19), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.

A Novel Nonsense Mutation in Leucine-Rich, Glioma-Inactivated-1 Gene as the Underlying Cause of Familial Temporal Lobe Epilepsy

Kanwal, Sumaira,Yoo, Da Hye,Tahir, Shahzad,Lee, Su Jung,Lee, Min Hee,Choi, Byung-Ok,Chung, Ki Wha 대한신경과학회 2018 Journal of Clinical Neurology Vol.14 No.4

Wide phenotypic variations in Charcot-Marie-Tooth 1A neuropathy with rare copy number variations on 17p12

Kanwal, Sumaira,Choi, Byung-Ok,Kim, Sang-Beom,Koo, Hea-Soo,Kim, Jee-Young,Hyun, Young-Se,Lee, Hye-Jin,Chung, Ki-Wha The Korean Society for Integrative Biology 2011 Animal cells and systems Vol.15 No.4

Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A) neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n=19), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.

A POLG2 Homozygous Mutation in an Autosomal Recessive Epilepsy Family Without Ophthalmoplegia

이수정,Sumaira Kanwal,유다혜,박혜리,최병옥,정기화 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.3

BAG3 mutation in a patient with atypical phenotypes of myofibrillar myopathy and Charcot–Marie–Tooth disease

김성주,남수현,Sumaira Kanwal,남다은,유다혜,채종희,서연림,정기화,최병옥 한국유전학회 2018 Genes & Genomics Vol.40 No.12

Bcl2-associated athanogene 3 (BAG3) mutations have been reported to cause the myofibrillar myopathy (MFM) which shows progressive limb muscle weakness, respiratory failure, and cardiomyopathy. Myopathy patients with BAG3 mutation are very rare. We described a patient showing atypical phenotypes. We aimed to find the genetic cause of Korean patients with sensory motor polyneuropathy, myopathy and rigid spine. We performed whole exome sequencing (WES) with 423 patients with sensory motor polyneuropathy. We found BAG3 mutation in one patient with neuropathy, myopathy and rigid spine syndrome, and performed electrophysiological study, whole body MRI and muscle biopsy on the patient. A de novo heterozygous p.Pro209Leu (c.626C>T) mutation in BAG3 was identified in a female myopathy. She first noticed a gait disturbance and spinal rigidity at the age of 11, and serum creatine kinase levels were elevated ninefolds than normal. She showed an axonal sensory-motor polyneuropathy like Charcot–Marie–Tooth disease (CMT), myopathy, rigid spine and respiratory dysfunction; however, she did not show any cardiomyopathy, which is a common symptom in BAG3 mutation. Lower limb MRI and whole spine MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. When we track traceable MRI 1 year later, the muscle damage progressed slowly. As far as our knowledge, this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.

Biallelic mutations in pakistani families with autosomal recessive prelingual nonsyndromic hearing loss

Choi Hee Ji,Kanwal Sumaira,Hameed Rashid,Tamanna Nasrin,Perveen Shazia,Mahreen Hina,Son Wonseok,Lee Kyung Suk,Chung Ki Wha 한국유전학회 2023 Genes & Genomics Vol.45 No.2

Background Nonsyndromic autosomal recessive hearing loss (DFNB) is an etiologically heterogeneous disorder group showing a wide spectrum of onset ages and severity. DFNB genes are very diverse in their types and functions, making molecular diagnosis difficult. DFNB is particularly frequent in Pakistan, which may be partly due to consanguinity. Objective This study was performed to determine the genetic causes in Pakistani DFNB families with prelingual onset and to establish genotype-phenotype correlation. Methods Whole exome sequencing and subsequent genetic analysis were performed for 11 Pakistani DFNB families including eight consanguineous families. Results We identified eight pathogenic or likely pathogenic mutations in LOXHD1, GJB2, SLC26A4, MYO15A, and TMC1 from six families. The GJB2 mutations were identified in two families each with compound heterozygous mutations and a homozygous mutation. The compound heterozygous mutations in LOXHD1 ([p.D278Y] + [p.D1219E]) and GJB2 [p.M1?] + [p.G12Vfs*2]) were novel. The four missense or start-loss mutations were located at well conserved residues, and most in silico analysis predicted their pathogenicity. In addition to causative mutations, we found compound heterozygous mutations in PTPRQ as variants of uncertain significance. Conclusion This study identified biallelic mutations as the underlying cause of early onset DFNB in six Pakistani families. This study will be helpful in providing an exact molecular diagnosis and treatment of prelingual onset deafness patients.

Association of <i>miR-149</i> polymorphism with onset age and severity in Charcot–Marie–Tooth disease type 1A

Nam, Soo Hyun,Kanwal, Sumaira,Nam, Da Eun,Lee, Min Hee,Kang, Tae Hoon,Jung, Sung-Chul,Choi, Byung-Ok,Chung, Ki Wha Elsevier 2018 Neuromuscular disorders Vol.28 No.6

<P><B>Abstract</B></P> <P>Charcot–Marie–Tooth disease type 1A (CMT1A) is caused by 1.5-fold increased dosage of the <I>PMP22</I>; however, onset age and severity vary considerably among patients. The exact reason behind these phenotypic heterogeneities has rarely been discovered yet. Because miRNAs are the key regulators of gene expression, we speculated that variants of miRNAs might be the genetic modifiers for CMT1A. This study noticed a common single nucleotide polymorphism (n.86T > C, rs2292832) in the <I>miR-149</I> which was predicted to target several CMT causing genes including <I>PMP22</I>. The rs2292832 was located near the 3′ end of the precursor microRNA of the <I>miR-149</I>. We performed an association study between the rs2292832 polymorphism and clinical phenotypes of CMT1A in subjects consisting of 176 unrelated Korean CMT1A patients and 176 controls. From this study, we observed that rs2292832 was closely associated to the onset age and severity of CMT1A. Particularly, the TC and CC genotypes were significantly associated with late onset and mild symptom. Therefore, we suggest that the rs2292832 variant in the <I>miR-149</I> is a potential candidate as a genetic modifier which affects the phenotypic heterogeneity of CMT1A. This study may provide the first evidence that polymorphism in the <I>miR</I> gene is associated with the CMT1A phenotype.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An association study was conducted between <I>miR-149</I> SNP and severity of CMT1A. </LI> <LI> The rs2292832 SNP was closely associated to the onset age and severity of CMT1A. </LI> <LI> The TC and CC genotypes were associated with late onset and mild symptom. </LI> <LI> The rs2292832 in <I>miR-149</I> was suggested as a potential genetic modifier of CMT1A. </LI> </UL> </P>

Phylogenetic Analysis of Mitochondrial DNA Control Region in the Swimming Crab, Portunus trituberculatus

Eun Min Cho,민기식,Sumaira Kanwal,현영세,박선화,정기화 한국통합생물학회 2009 Animal cells and systems Vol.13 No.3

The control region of mitochondrial DNA (13516- 14619) is located between srRNA and tRNAlle gene in swimming crab, Portunus trituberculatus. The present study was investigated the genetic polymorphisms of the control region in samples of P. trituberculatus collected at coastal waters of the Yellow Sea in Korea. A total of 300 substitution and indel polymorphic sites were identified. In addition to SNPs and indel variation, a hypervariable microsatellite motif was also identified at position from 14358 to 14391, which exhibited 10 alleles including 53 different suballeles. When the hypervariable microsatellite motif was removed from the alignment, 95 haplotypes were identified (93 unique haplotypes). The nucleotide and haplotype diversities were ranged from 0.024 to 0.028 and from 0.952 to 1.000, respectively. The statistically significant evidence for geographical structure was not detected from the analyses of neighbor-joining tree and minimum-spanning network, neither. This result suggest that population of P. trituberculatus are capable of extensive gene flow among populations. We believed that the polymorphisms of the control region will be used for informative markers to study phylogenetic relationships of P. trituberculatus.

Phylogenetic Analysis of Mitochondrial DNA Control Region in the Swimming Crab, Portunus trituberculatus

Cho, Eun-Min,Min, Gi-Sik,Kanwal, Sumaira,Hyun, Young-Se,Park, Sun-Wha,Chung, Ki-Wha The Korean Society for Integrative Biology 2009 Animal cells and systems Vol.13 No.3

The control region of mitochondrial DNA (13516-14619) is located between srRNA and $tRNA^{lle}$ gene in swimming crab, Portunus trituberculatus. The present study was investigated the genetic polymorph isms of the control region in samples of P. trituberculatus collected at coastal waters of the Yellow Sea in Korea. A total of 300 substitution and indel polymorphic sites were identified. In addition to SNPs and indel variation, a hypervariable microsatellite motif was also identified at position from 14358 to 14391, which exhibited 10 alleles including 53 different suballeles. When the hypervariable microsatellite motif was removed from the alignment, 95 haplotypes were identified (93 unique haplotypes). The nucleotide and haplotype diversities were ranged from 0.024 to 0.028 and from 0.952 to 1.000, respectively. The statistically significant evidence for geographical structure was not detected from the analyses of neighbor-joining tree and minimum-spanning network, neither. This result suggest that population of P. trituberculatus are capable of extensive gene flow among populations. We believed that the polymorph isms of the control region will be used for informative markers to study phylogenetic relationships of P. trituberculatus.

Effect of pyrolysis temperature on the physiochemical properties of biochars produced from raw and fermented rice husks

Hafiza Sana,Riaz Asim,Arshad Zubaria,Zahra Syeda Tahsin,Akhtar Javaid,Kanwal Sumaira,Zeb Hassan,Kim Jaehoon 한국화학공학회 2023 Korean Journal of Chemical Engineering Vol.40 No.8

This study investigated the slow pyrolysis behavior of raw rice husk (RRH) and fermented rice husk (FRH) in a fixed-bed reactor at temperatures in the range of 200–600 °C. The effects of pyrolysis temperature on the biochar yield, composition, and physiochemical properties were examined to evaluate the energy potential of biochars produced from RRH and FRH. The FRH-derived biochar produced at 600 °C was found to be more suitable than the RRH-derived biochar because of its higher carbon content (68.9% vs 42.1%), GCV (31.6 vs 24.1 MJ kg−1), and true density (1.94 vs 1.54 g cm −3). The slow pyrolysis in the high-temperature regime facilitated the formation of lignin-rich and aromatically condensed biochar, making it particularly useful for producing carbon-rich materials. Thus, slow pyrolysis can be a technically viable approach for producing high-energy-density solid fuels that can replace medium-ranking coals in co-firing.